Triethylamine → Nepsilon-Benzyloxycarbonyl-Nalpha-(tert-butoxycarbonyl)-L-lysyl-L-phenylalanyl-L-leucine ethyl ester

HRID 1090011Notes

Reaction equation

HRID 1090011 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:10][C:11](=[O:29])[C@H:12]([CH2:25][CH:26]([CH3:28])[CH3:27])[NH:13][C:14](=[O:24])[C@H:15]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[NH2:16])[CH3:9].C(N(CC)CC)C.[CH2:37]([O:44][C:45]([NH:47][CH2:48][CH2:49][CH2:50][CH2:51][C@@H:52]([C:61](O)=[O:62])[NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[O:46])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)(Cl)Cl>[CH2:8]([O:10][C:11](=[O:29])[C@H:12]([CH2:25][CH:26]([CH3:28])[CH3:27])[NH:13][C:14](=[O:24])[C@H:15]([CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[NH:16][C:61](=[O:62])[C@H:52]([CH2:51][CH2:50][CH2:49][CH2:48][NH:47][C:45]([O:44][CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:46])[NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:58])[CH3:59])=[O:55])[CH3:9]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 2724765Boc-Lys(Z)-OHHCID 67716275HCID 67716275, compound

Product 1

HCID 15021173Nepsilon-Benzyloxycarbonyl-Nalpha-(tert-butoxycarbonyl)-L-lysyl-L-phenylalanyl-L-leucine ethyl esterYield 92.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of 1.68 g (4 mmol) of L-phenylalanyl-L-leucine ethyl ester trifluoroacetate, 0.56 mL (4 mmol) of triethylamine and 32 mL of chloroform were added at 0° C., first 1.52 g (4 mmol) of Nε -benzyloxycarbonyl-Nα -(tert-butoxycarbonyl)-L-lysine, and then 0.83 g (4 mmol) of dicyclohexylcarbodiimide, each being added in a single portion. The reaction mixture was warmed gradually to room temperature and then stirred overnight at that temperature. The precipitate which formed was removed by filtration. The filtrate was evaporated in vacuo and the residue was chromatographed on silica gel using 3:1 methylene chloride/ethyl acetate as eluent to give 2.48 g (92.7%) of the title compound as a white solid melting at 135°-136° C. after crystallization from a mixture of ethyl acetate and isopropyl ether. The product has the structural formula: ##STR113## as further confirmed by NMR, IR and elemental analyses.

Workup

  1. additionwere added at 0° C.
  2. customThe precipitate which formed
  3. customwas removed by filtration
  4. customThe filtrate was evaporated in vacuo
  5. customthe residue was chromatographed on silica gel using 3:1 methylene chloride/ethyl acetate as eluent

Sources & evidence

ORD record
ord-c3934d36052f44c5b1f1394f06ca0083
Source dataset
uspto-grants-1992_01
Patent number
US05079366

Reaction notes

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